STROKE Professor Iqbal Singh OBE FRCP Stroke? ACT FAST National - - PowerPoint PPT Presentation

STROKE

Professor Iqbal Singh OBE FRCP

Stroke? → ACT FAST

National Stroke Strategy QM1, Raising Awareness, QM2 Time is Brain

Clinical presentations of stroke ▪ Acute onset combination of

➢Face / arm / leg weakness or sensory loss ➢Loss of co-ordination ➢Speech disturbance ➢Visual disturbance

▪ Acute onset does not mean total deficit within seconds ▪ Most TIAs are < 20 minutes

• Stroke varies
• All begin suddenly
• ¼ patients do not leave hospital
• ⅓ survivors need help every day due to:

➢ Weakness ➢ Speech problems ➢ Swallowing problems ➢ Visual problems ➢ Memory problems

• Urgent recognition & stroke unit admission improves

recovery

Background Information

• Incidence of stroke now higher than that of acute

coronary syndromes

• For 1 million inhabitants ,

There will be 2400 strokes per year (1800 first-ever, 600 recurrent or after TIA)

Of these

– 700 (29%) will die – 600 (25%) will be dependent – 1100 (46%) will be independent Background Information

Collecting information about patient outcomes at six months enables us to look at: changes in functional outcome and place of residence change in AF status and anticoagulation to improve secondary prevention mood and cognition, in particular identification of these areas which were silent symptons when the patient presented acutely. It is one of the CCG Outcomes Indicator Set (OIS) and was mandated in the National Stroke Strategy. By contributing this information to the audit it will for the first time allow us to assess outcomes at six months both nationally and for individual teams.

SSNAP Aug-Nov 2016

Why collecting six month assessment data is important

Causes of Ischaemic Stroke

Carotid Artery Stenosis

Common Carotid External Carotid Stenosis at bifurcation

• f Internal Carotid



European carotid trialists collaborative group



European Carotid Surgery Trial (ECST)



North American symptomatic carotid endarterectomy trial I & II(NASCET)  3 RCT’s (symptomatic) – 6143 pts  Severe Stenosis RRR 48% NNT 15

Carotid Endarterectomy

AF is is th the most common su sustained cardiac arr rrhythmia1

1.

• 1. Camm et al. Eur Heart J 2010;31:2369–429;

2.

• 2. NHS choices. Atrial fibrillation. http://www.nhs.uk/Conditions/Atrial-fibrillation/Pages/Introduction.aspx. Accessed November 2016;
• 3. Go et al. JAMA 2001;285:2370–2375; 4. Savelieva et al. Clin Cardiol 2008;31:55–62.

Prevalence in the general population1 Europeans suffer from AF, including an estimated 1 million in the UK2 Greater risk in men than women (adjusted for age and risk factors)2,3 Lifetime risk in those who reach 40 years of age1

1–2% >6 million1 1.4 x ~25% Incidence is projected to grow significantly4

AF: atrial fibrillation.

• Estimated annual burden of AF (2008 data)1:
• Also contributing to the burden of AF are2:
• Indirect costs, for example loss of time in employment
• Cost related to co-morbidities of AF, e.g. stroke
• Direct costs of all strokes to the NHS in England are estimated at £2.8 billion3
• AF is responsible for 20% of all strokes4
• AF-related strokes are more severe5
• Severe strokes are >3x more costly on average than typical mild strokes6

Burden of f AF and rela lated str troke

1.

• 1. The Office of Health Economics Estimating the direct costs of atrial fibrillation to the NHS in the constituent countries of the UK and at SHA level in England, 2008. Accessed November 2016;

2.

• 2. Blomstrom Lundqvist et al. Europace 2011;13:ii9–12; 3. Quality Standards Programme. NICE cost impact and commissioning assessment: quality standard for stroke.

June 2010. https://www.nice.org.uk/guidance/qs2/resources/cost-impact-and-commissioning-assessment-252272845. Accessed November 2016;

• 4. Marini et al. Stroke 2005;36:1115–1119; 5. Jorgensen et al. Stroke 1996;27:1765–1769; 6. Szucs and Bramkamp. J Thromb Haemost 2006;4:1180–1185.

Total direct cost to NHS 5.7 million hospital bed days Non-bed inpatient costs Outpatient costs £2.2 billion £1.8 billion £124 million £205 million

AF: atrial fibrillation; NHS: National Health Service.

Effecti tive AF tr treatm tment: t: Estim timati ting th the potential im impact of f in inadequate tr treatm tment

1.

• 1. Townsend et al. Coronary heart disease statistics 2012 edition. British Heart Foundation. 2012;

2.

• 2. Marini et al. Stroke 2005;36:1115–1119; 3. Hart et al. Ann Intern Med 2007;146:857–867;
• 4. Connolly et al. Circulation 2007;116:449–555.

152,000 strokes annually in the UK1 30,400 are due to AF 19,456 are preventable with warfarin therapy

20% of strokes due to AF2

~6,485 strokes may occur annually in the UK as a result of a lack of appropriate treatment

~66% of eligible patients treated with warfarin4 – 33% do not receive warfarin treatment RRR of 64% with warfarin vs no treatment3

AF: atrial fibrillation; RRR: relative risk reduction.

Apixaban1,2 Rivaroxaban1,3 Dabigatran1,4 Edoxaban5 Mechanism of action Direct factor Xa inhibitor Direct factor Xa inhibitor Direct thrombin inhibitor Direct factor Xa inhibitor Oral bioavailability ~50% 80–100% ~6.5% ~62% Pro-drug No No Yes No Food effect No Yes (20 mg and 15 mg doses need to be taken with food) No No Renal clearance ~27% ~33 %* 85% 50%† Mean half-life (t1/2) 12 h 5–9 h (young) 11–13 h (elderly) 12–18 h (patients)‡ 10–14 h Tmax 3–4 h 2–4 h 0.5–2 h 1–2 h

Cli linical pharmacology of f NOACs

• 1. Ansell. Hematology Am Soc Hematol Educ Program. 2010:221–228; 2. Apixaban SmPC. Available at http://www.medicines.org.uk;
• 3. Rivaroxaban SmPC. Available at http://www.medicines.org.uk; 4. Dabigatran SmPC. Available at http://www.medicines.org.uk;
• 5. Edoxaban SmPC. Available at http://www.medicines.org.uk.

*Direct renal excretion as unchanged active substance. †35% of administered dose. ‡Prolonged in patients with impaired renal function. The information in this table is based on the SmPC for apixaban, rivaroxaban, dabigatran and edoxaban. Please refer to the SmPC for further information.

NOAC: non-vitamin K antagonist oral anticoagulant.

An in independent, retr trospective USA rea eal-world analysis1

• 1. Yao et al. J Am Heart Assoc. 2016;5:e003725.

Non-interventional retrospective analysis using administrative claims from Optumlabs Data Warehouse database and Medicare Advantage Study population

• Adult patients prescribed oral anticoagulants

from 1 October 2010–30 June 2015*

• All patients were required to have at least one

inpatient or outpatient AF diagnosis at either primary or secondary positions (ICD-9 diagnosis code 427.31) on the index date or at baseline

Rivaroxaban vs warfarin n = 32,350 Dabigatran vs warfarin n = 28,614 Apixaban vs warfarin n = 15,390

Analysis

• Cox proportional hazards regression was used to

compare outcomes in each of the propensity score matched cohorts Study endpoints

• Primary effectiveness outcome: stroke or systemic

embolism, including ischaemic stroke, haemorrhagic stroke, and systemic embolism.

• Primary safety outcome: major bleeding,

including gastrointestinal bleeding, intracranial bleeding, and bleeding from other sites.

The definitions of efficacy and safety endpoints in the ARISTOTLE, RE-LY and ROCKET-AF clinical trials differed to those in the USA real-world analysis.

There are no head-to-head clinical trials comparing the NOACs, so it is not appropriate to compare the results for different products across clinical trials, as trials have different designs and can vary greatly in terms of key parameters, e.g. patient populations. Three matched cohorts using 1:1 propensity score matching vs warfarin

 The effectiveness and safety of apixaban, dabigatran, and rivaroxaban were compared for stroke prevention in NVAF patients, in the largest USA contemporary evaluation comparing NOACs and warfarin to date

FDA: Food and Drug Administration; ICD: International Classification of Diseases; NOAC: non-VKA oral anticoagulant; NVAF: non -valvular atrial fibrillation.

*The USA real-world analysis did not include edoxaban, as it was not yet FDA approved during the time periods analysed

NIC ICE Cli linical Guid ideli line 182 rec ecommendations for r anticoagulants in in patients wit ith CKD and NVAF1

Anti ticoagulants

• The NICE Clinical Guideline 182 recommendations for anticoagulant therapy in patients

with CKD and NVAF is as follows:

• Consider apixaban in preference to warfarin in people with a confirmed

eGFR of 30–50 mL/min/1.73 m2 and non-valvular atrial fibrillation who have one or more of the following risk factors:

• Prior stroke or transient ischaemic attack
• Age ≥75 years
• Hypertension
• Diabetes mellitus
• Symptomatic heart failure
• 1. NICE guidelines (CG182). Chronic kidney disease (partial update). Early identification and management of
• f chronic kidney disease in adults in primary and secondary care. July 2014.

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; NICE: National Institute of Health and Care Excellence; NVAF, non-valvular atrial fibrillation.

• NOACs provide predictable, stable and reliable levels of

anticoagulation1–4

• Data from both RCTs and real world sources have

demonstrated that NOACs are comparable to or superior to warfarin/VKA in terms of risk reduction for stroke / systemic embolism and rates of major bleeding in patients with NVAF1–6

• NICE and ESC guidelines support the use of NOACs in

appropriate patients with NVAF7–9

• 1. Connolly et al. N Engl J Med. 2009;361:1139–1151; 2. Patel et al. N Engl J Med. 2011;365:883–891; 3. Granger et al. N Engl J Med. 2011;365:981–992; 4. Giugliano et al.

N Engl J Med. 2013;369:2093–2104; 5. Yao et al. J Am Heart Assoc. 2016;5:e003725; 6. Hohnloser et al. Presentation at ESC Congress 2016, Poster 87551.

• 7. NICE guidelines (CG180) Atrial fibrillation: the management of atrial fibrillation. June 2014; 8. NICE technology appraisal guidance 355. Edoxaban for preventing stroke

and systemic embolism in people with non-valvular atrial fibrillation. September 2015; 9. Kirchhof et al. Eur Heart J. 2016. Pii: ehw210. [Epub ahead of print].

CI: confidence interval; ESC: European Society of Cardiology; NICE: National Institute for Health and Care Excellence; NOAC: non-vitamin K antagonist oral anticoagulant; NVAF: non-valvular atrial fibrillation; RCTs: randomised control trials; VKA: vitamin K antagonist.

PP-ELI-GBR-2312 Date of preparation: November 2017

• 1. State of the Nation: stroke statistics January 2017. Available at: www.stroke.org.uk. Last accessed: November 2017.

There are over 100,000 strokes annually in the UK1

AF is a contributing factor in up to 1 in 5 strokes in the UK1 In the UK, 24% of eligible patients with AF do not receive anticoagulation1

It is estimated that if AF were adequately treated, around 7,000 strokes would be prevented and over

2,000 lives saved every year in England alone1

Only 45% of people with known AF who are admitted to hospital with stroke are

• n anticoagulation1

Effective treatment of AF could save >2,000 lives in the UK every year1

About 85% of all strokes are ischaemic and 15% are haemorrhagic1

PP-ELI-GBR-2312 Date of preparation: November 2017

• 1. Apixaban SmPC. Available at: www.medicines.org.uk; 2. Dabigatran SmPC. Available at: www.medicines.org.uk;
• 3. Rivaroxaban SmPC. Available at: www.medicines.org.uk; 4. Edoxaban SmPC. Available at: www.medicines.org.uk;

Factor Xa activation Thrombin generation Platelet activation Fibrin formation Venous thrombosis

Blood flow stasis

Dabigatran Apixaban Rivaroxaban Edoxaban

Arterial thrombosis

Plaque rupture

 Rapid onset of action  No significant food interactions  Low potential for drug–drug interactions  No requirement for routine coagulation monitoring  Practical concerns:

– Risk of bleeding in specific patient groups, such as older patients with renal dysfunction

NOACs have advantages over warfarin1–5

PP-ELI-GBR-1828 Date of preparation: November 2017

Regular follow-up and patient education helps to optimise treatment outcomes

• 1. Kirchhof P, et al. Eur Heart J 2016;37(38):28932962; 2. Apixaban SmPC. Available at: http://www.medicines.org.uk;
• 3. Dabigatran SmPC. Available at: http://www.medicines.org.uk; 4. Rivaroxaban SmPC. Available at: http://www.medicines.org.uk;
• 5. Edoxaban SmPC. Available at: http://www.medicines.org.uk.

*Class of evidence; †Level of evidence. AF: atrial fibrillation; CKD: chronic kidney disease; OAC: oral anticoagulant; SE: systemic embolism.

Patient education

Tailored patient education is recommended in all phases of AF management to support patients’ perception of AF and to improve management1 I C

Renal function

All AF patients treated with oral anticoagulation should be considered for at least yearly evaluation of renal function to detect CKD1

IIa B

Elderly patients

Elderly AF patients are at higher risk of stroke and, thus are more likely to benefit from an OAC than younger patients. Integrated AF management and careful adaptation of drug dosing (in accordance with the SmPC) should be used to reduce the complications of treatment in elderly patients1 Class* Level†

Follow-up and monitoring

Class* Level†

NOACs are all licensed for the prevention of stroke/SE in NVAF, and should be prescribed in accordance with the relevant SmPC25

PP-ELI-GBR-1828 Date of preparation: November 2017

Warfarin1 Apixaban2,3 Dabigatran2,4 Rivaroxaban2,5 Edoxaban6

Mechanism of action Inhibitor of vitamin K- dependent factors Direct factor Xa inhibitor Direct thrombin inhibitor Direct factor Xa inhibitor Direct factor Xa inhibitor Oral bioavailability >95% ~50% ~6.5% 80–100% ~62% Pro-drug No No Yes No No Food effect Yes (foods high in vitamin K may affect anticoagulation effect) No No Yes (20 mg and 15 mg doses need to be taken with food) No Renal clearance 8% ~27% 85% ~33%* 50%† Mean half-life (t1/2) 40 hours 12 hours 12–18 hours‡ 5–9 hours (young) 11–13 hours (elderly) 10–14 hours Time to reach peak plasma concentration (Tmax) Within 4 hours, but peak anticoagulation effect may require 7296 hours§ 3–4 hours 0.5–2 hours 2–4 hours 1–2 hours

Clinical pharmacology of warfarin and the NOACs

• 1. Warfarin SmPC. Available at: http://www.medicines.org.uk; 2. Ansell J. Hematology Am Soc Hematol Educ Program 2010:2010;221–228;
• 3. Apixaban SmPC. Available at: http://www.medicines.org.uk; 4. Dabigatran SmPC. Available at: http://www.medicines.org.uk;
• 5. Rivaroxaban SmPC. Available at: http://www.medicines.org.uk; 6. Edoxaban SmPC. Available at: http://www.medicines.org.uk.

*Direct renal excretion as unchanged active substance;5 †35% of administered dose; 6 ‡Mean half-life prolonged in patients with impaired renal function;4

§In patients with impaired renal function.1

NOAC: non-vitamin K antagonist oral anticoagulant; SmPC: Summary of Product Characteristics.

Please refer to the appropriate product SmPCs for further information

PP-ELI-GBR-1828 Date of preparation: November 2017

Looking to the future: the effective management of ischaemic stroke in AF1

• 1. Lichten CA, et al. Rand Health Q.2015;5(2):2.

ECG: electrocardiogram.

Improved detection Better management Superior

• utcomes
• Increase awareness of the link between

AF and preventable stroke

• Reduce under-diagnosis by
• pportunistically screening at-risk

patients with a manual pulse check and follow-up ECG if indicated

• Reduced occurrence of

preventable stroke and mortality

• Reduced need for inpatient

hospitalisation

• Patient education to optimise compliance
• Provision of personalised care
• Continuity of care between care settings
• Appropriate anticoagulation therapy to reduce the

risk of AF-related stroke, taking into account use of NOACs in NVAF